A Comparative Study of the Triglycerides/HDL Ratio and Pseudocholinesterase Levels in Patients with Bladder Cancer

Background: Lipid alterations may serve as potential tumour biomarkers. The ratio of triglycerides to HDL cholesterol (TG/HDL ratio) is associated with various cancers. Pseudocholinesterase (PChE) activity, involved in TG hydrolysis, plays an important role in the metabolism of lipoprotein. There is scarce data assessing the reliability of both the TG/HDL ratio and PChE levels in correctly classifying patients suffering from bladder cancer. Methods: Three hundred and ninety-six patients undergoing cystoscopy or transurethral resection of the bladder (TURB), broken into two major groups, i.e., patients with histologically confirmed, non-metastatic bladder cancer (n = 208) and without bladder cancer (no bladder cancer, n = 188), formed the study population. The last group was split into two subgroups consisting of a cohort of patients never suffering from bladder cancer but with other bladder diseases (no CaBD, n = 100) and another cohort formed by patients characterised by eradicated bladder cancer after TURB with no recurrence during a three-month follow-up (previous bladder cancer, n = 88). Pieces of information by both metabolic derangement (the presence of type 2 diabetes mellitus), hypertension and lipid profile were retrieved from patient records upon entry to the study. Sensitivity, specificity, areas under the ROC (AUROC) of the TG/HDL ratio, and PChE levels were used in diagnostic decision making. Results: The TG/HDL ratio as well as PChE concentrations of bladder cancer patients were significantly different when compared to those with previous bladder cancer and the no CaBD patients (p = 0.023 and 0.0004, respectively). There was an independent role of both the TG/HDL ratio and PChE levels in predicting the presence of bladder cancer (OR: 1.22 and 0.99, respectively), but the reliability of the TG/HDL ratio (AUROC: 0.587) was superior to that of PChE levels (AUROC: 0.374). The AUROC of a new parameter resulting from the combination of the TG/HDL ratio with PChE levels showed a further increment in the discriminant power of the bladder cancer presence (0.6298), interestingly with a negative predictive value (89%) according to the Bayesian approach. The cut-off of the TG/HDL ratio, the main marker of the present study that better distinguishes bladder cancer from no bladder cancer patients, was 2.147. Discussion and Conclusions: The reliability of the TG/HDL ratio is based on the fact that this parameter likely mirrors the insulin resistance (IR) underlying bladder cancer patients. Furthermore, PChE levels evidence both IR and the associated non-alcoholic fatty liver disease. The TG/HDL ratio and PChE levels as well as their combined use could help physicians to assess/confirm the presence of this very common cancer, where early detection is important to ensure the best therapeutical approach

Rapid and safe response to low-dose carbamazepine in neonatal epilepsy

To evaluate treatment responses in benign familial neonatal epilepsy (BFNE)

Augmented Reticular Thalamic Bursting and Seizures in Scn1a-Dravet Syndrome

Loss of function in the Scn1a gene leads to a severe epileptic encephalopathy called Dravet syndrome (DS). Reduced excitability in cortical inhibitory neurons is thought to be the major cause of DS seizures. Here, in contrast, we show enhanced excitability in thalamic inhibitory neurons that promotes the non-convulsive seizures that are a prominent yet poorly understood feature of DS. In a mouse model of DS with a loss of function in Scn1a, reticular thalamic cells exhibited abnormally long bursts of firing caused by the downregulation of calcium-activated potassium SK channels. Our study supports a mechanism in which loss of SK activity causes the reticular thalamic neurons to become hyperexcitable and promote non-convulsive seizures in DS. We propose that reduced excitability of inhibitory neurons is not global in DS and that non-GABAergic mechanisms such as SK channels may be important targets for treatment

The ILAE classification of seizures and the epilepsies: Modification for seizures in the neonate. Position paper by the ILAE Task Force on Neonatal Seizures

Seizures are the most common neurological emergency in the neonatal period and in contrast to those in infancy and childhood, are often provoked seizures with an acute cause and may be electrographic‐only. Hence, neonatal seizures may not fit easily into classification schemes for seizures and epilepsies primarily developed for older children and adults. A Neonatal Seizures Task Force was established by the International League Against Epilepsy (ILAE) to develop a modification of the 2017 ILAE Classification of Seizures and Epilepsies, relevant to neonates. The neonatal classification framework emphasizes the role of electroencephalography (EEG) in the diagnosis of seizures in the neonate and includes a classification of seizure types relevant to this age group. The seizure type is determined by the predominant clinical feature. Many neonatal seizures are electrographic‐only with no evident clinical features; therefore, these are included in the proposed classification. Clinical events without an EEG correlate are not included. Because seizures in the neonatal period have been shown to have a focal onset, a division into focal and generalized is unnecessary. Seizures can have a motor (automatisms, clonic, epileptic spasms, myoclonic, tonic), non‐motor (autonomic, behavior arrest), or sequential presentation. The classification allows the user to choose the level of detail when classifying seizures in this age group

DNM1 encephalopathy: A new disease of vesicle fission.

ObjectiveTo evaluate the phenotypic spectrum caused by mutations in dynamin 1 (DNM1), encoding the presynaptic protein DNM1, and to investigate possible genotype-phenotype correlations and predicted functional consequences based on structural modeling.MethodsWe reviewed phenotypic data of 21 patients (7 previously published) with DNM1 mutations. We compared mutation data to known functional data and undertook biomolecular modeling to assess the effect of the mutations on protein function.ResultsWe identified 19 patients with de novo mutations in DNM1 and a sibling pair who had an inherited mutation from a mosaic parent. Seven patients (33.3%) carried the recurrent p.Arg237Trp mutation. A common phenotype emerged that included severe to profound intellectual disability and muscular hypotonia in all patients and an epilepsy characterized by infantile spasms in 16 of 21 patients, frequently evolving into Lennox-Gastaut syndrome. Two patients had profound global developmental delay without seizures. In addition, we describe a single patient with normal development before the onset of a catastrophic epilepsy, consistent with febrile infection-related epilepsy syndrome at 4 years. All mutations cluster within the GTPase or middle domains, and structural modeling and existing functional data suggest a dominant-negative effect on DMN1 function.ConclusionsThe phenotypic spectrum of DNM1-related encephalopathy is relatively homogeneous, in contrast to many other genetic epilepsies. Up to one-third of patients carry the recurrent p.Arg237Trp variant, which is now one of the most common recurrent variants in epileptic encephalopathies identified to date. Given the predicted dominant-negative mechanism of this mutation, this variant presents a prime target for therapeutic intervention

Early recognition of characteristic conventional and amplitude-integrated EEG patterns of seizures in <i>SCN2A </i>and <i>KCNQ3</i>-related epilepsy in neonates

Purpose: Early recognition of seizures in neonates secondary to pathogenic variants in potassium or sodium channel coding genes is crucial, as these seizures are often resistant to commonly used anti-seizure medications but respond well to sodium channel blockers. Recently, a characteristic ictal amplitude-integrated electroencephalogram (aEEG) pattern was described in neonates with KCNQ2-related epilepsy. We report a similar aEEG pattern in seizures caused by SCN2A- and KCNQ3-pathogenic variants, as well as conventional EEG (cEEG) descriptions. Methods: International multicentre descriptive study, reporting clinical characteristics, aEEG and cEEG findings of 13 neonates with seizures due to pathogenic SCN2A- and KCNQ3-variants. As a comparison group, aEEGs and cEEGs of neonates with seizures due to hypoxic-ischemic encephalopathy (n = 117) and other confirmed genetic causes affecting channel function (n = 55) were reviewed. Results: In 12 out of 13 patients, the aEEG showed a characteristic sequence of brief onset with a decrease, followed by a quick rise, and then postictal amplitude attenuation. This pattern correlated with bilateral EEG onset attenuation, followed by rhythmic discharges ending in several seconds of post-ictal amplitude suppression. Apart from patients with KCNQ2-related epilepsy, none of the patients in the comparison groups had a similar aEEG or cEEG pattern. Discussion: Seizures in SCN2A- and KCNQ3-related epilepsy in neonates can usually be recognized by a characteristic ictal aEEG pattern, previously reported only in KCNQ2-related epilepsy, extending this unique feature to other channelopathies. Awareness of this pattern facilitates the prompt initiation of precision treatment with sodium channel blockers even before genetic results are available.</p

The ILAE classification of seizures and the epilepsies : Modification for seizures in the neonate. Position paper by the ILAE Task Force on Neonatal Seizures

Seizures are the most common neurological emergency in the neonatal period and in contrast to those in infancy and childhood, are often provoked seizures with an acute cause and may be electrographic-only. Hence, neonatal seizures may not fit easily into classification schemes for seizures and epilepsies primarily developed for older children and adults. A Neonatal Seizures Task Force was established by the International League Against Epilepsy (ILAE) to develop a modification of the 2017 ILAE Classification of Seizures and Epilepsies, relevant to neonates. The neonatal classification framework emphasizes the role of electroencephalography (EEG) in the diagnosis of seizures in the neonate and includes a classification of seizure types relevant to this age group. The seizure type is determined by the predominant clinical feature. Many neonatal seizures are electrographic-only with no evident clinical features; therefore, these are included in the proposed classification. Clinical events without an EEG correlate are not included. Because seizures in the neonatal period have been shown to have a focal onset, a division into focal and generalized is unnecessary. Seizures can have a motor (automatisms, clonic, epileptic spasms, myoclonic, tonic), non-motor (autonomic, behavior arrest), or sequential presentation. The classification allows the user to choose the level of detail when classifying seizures in this age group.Peer reviewe

Why monitor the neonatal brain-that is the important question

A key goal of neonatal neurocritical care is improved outcomes, and brain monitoring plays an essential role. The recent NEST trial(1) reported no outcome benefits using aEEG monitoring compared to clinical seizure identification among neonates treated for seizures. However, the study failed to prove the effects of monitoring on seizure treatment in the first place.Non peer reviewe